Human papilloma virus type 16 (HPV-16), herpes simplex virus type 2 (HSV-2) and human cytomegalovirus have been linked to cervical cancer. We examined whether HSV-2 and HPV-16 DNA sequences can transform early passage human cells. Gingival fibroblasts derived from a normal individual (N-16) and from a hyperplastic gingival tissue of an epileptic patient (R-30) treated with phenytoin were transfected with HPV-16 DNA alone or in combination with HSV-2 DNA. HPV-16 DNA efficiently immortalized R-30 cells but not N-16 cells. R-30 cells co- transfected with HPV-16 and HSV-2 DNAs were more aneuploid and grew better in soft agar than R-30 transfected with HPV-16 DNA alone. Both HSV-2 and HPV-16 DNA sequences were detected by Southern blot and PCR analysis in transformed cells. We have published a paper with these data. We will examine the expression of E6 and E7 genes of HPV and activation of cellular oncogenes in these transformants. We would also like to pursue similar studies with HCMV DNA sequences. These data suggest that HPV-16 and HSV-2 DNA sequences can cooperate in multistep process of transformation.